Process for the preparation of arylamides of heteroaromatic carboxylic acids

ABSTRACT

A process for the preparation of arylamides of heteroaromatic carboxylic acids of the formula: ##STR1## in which each A n  is nitrogen or CR n  (n=1 to 5), with the proviso that at least one of the ring members is nitrogen and that two nitrogen atoms are not bonded directly to one another; R 1  to R 5 , if present, independently of one another are hydrogen, C 1-4  -alkyl or aryl, one of the substituents R 1  to R 5  being a group of the formula --OR, in which R is an optionally substituted aromatic or heteroaromatic radical; R 6  is hydrogen or C 1-4  -alkyl; and R 7  is an optionally substituted aromatic or heteroaromatic radical. The amides are obtained from the corresponding heteroaromatic halogen compounds, the corresponding aromatic amines and carbon monoxide in the presence of a palladium phosphine complex. Compounds of this class are important herbicides.

This application is a continuation-in-part of U.S. Ser. No. 08/850,393,filed on May 2, 1997.

BACKGROUND OF THE INVENTION

1. Field Of The Invention

The invention relates to a process for the preparation of arylamides ofheteroaromatic carboxylic acids by reacting heteroaromatic halogencompounds with carbon monoxide and aromatic amines in the presence of acatalyst and a base. The invention further relates to a novelhalogenopyridine as a starting material for the preparation, accordingto the invention, of an arylamide.

The amides which can be prepared according to the invention have thegeneral formula: ##STR2## in which: A¹ is nitrogen or CR¹,

A² is nitrogen or CR²,

A³ is nitrogen or CR³,

A⁴ is nitrogen or CR⁴ and

A⁵ is nitrogen or CR⁵,

with the proviso that at least one of the ring members A¹ to A⁵ isnitrogen and that two nitrogen atoms are not bonded directly to oneanother;

R¹ to R⁵, if present, independently of one another are hydrogen, C₁₋₄-alkyl or aryl, but one of the substituents R¹ to R⁵ is a group of theformula --OR, in which R is an optionally substituted aromatic orheteroaromatic radical;

R⁶ is hydrogen or C₁₋₄ -alkyl; and

R⁷ is an optionally substituted aromatic or heteroaromatic radical.

Said amides include especially the arylamides of pyridine-, pyrimidine-,pyrazine- and 1,3,5-triazinecarboxylic acids.

2. Background Art

Numerous compounds of the structure of formula I, especially those inwhich one of the substituents R¹ to R⁵ is an aryloxy group (--OR)adjacent to a ring nitrogen atom, are important herbicides(International Published Patent Application No. 94/27974, EuropeanPublished Patent Application No. 0,053,011 and European Published PatentApplication No. 0,447,004). The synthesis of these known compounds isconventionally based on the corresponding carboxylic acids or carboxylicacid derivatives (acid chlorides, esters, nitriles), although these areoften difficult to obtain and therefore expensive.

BROAD DESCRIPTION OF THE INVENTION

The main object of the invention was to provide an alternative processbased on more easily obtainable educts. Other objects and advantages ofthe invention are set out herein or are obvious herefrom to one skilledin the art.

The objects and advantages of the invention are achieved by theprocesses and compound of the invention.

It has been found that halogen compounds of the general formula:##STR3## in which A¹ to A⁵ are as defined above and X is chlorine,bromine or iodine, react directly with carbon monoxide and a primary orsecondary amine of the general formula:

    R.sup.6 --NH--R.sup.7                                      III,

in which R⁶ and R⁷ are as defined above, in the presence of a base, togive a good to almost quantitative yield of the desired products (I)when a complex of palladium with a triphenylphosphine of the generalformula: ##STR4## in which R⁸ to R¹⁰ independently of one another areC₁₋₄ -alkyl, C₁₋₄ -alkoxy, benzyloxy or fluorine, is present as acatalyst.

The presence of the substituents R⁸ to R¹⁰ in the 4-position (paraposition) of the phenyl groups has proved to be an essential featurehere. The corresponding ortho-substituted and meta-substitutedcompounds, like the unsubstituted triphenylphosphine, give considerablypoorer yields or no product at all.

DETAILED DESCRIPTION OF THE INVENTION

Herein, C₁₋₄ -alkyl is to be understood as meaning any linear orbranched primary, secondary or tertiary alkyl groups having up to 4carbon atoms. Herein, aromatic or heteroaromatic radicals are to beunderstood as meaning especially monocyclic or polycyclic systems, suchas, phenyl, naphthyl, biphenylyl, anthracenyl, furyl, pyrrolyl,pyrazolyl, thiophenyl, pyridyl, indolyl or quinolinyl. These can carryone or more identical or different substituents, for example, loweralkyl groups such as methyl, halogenated alkyl groups such astrifluoromethyl, lower alkoxy groups such as methoxy, or lower alkylthio(alkanesulfanyl) or alkanesulfonyl groups such as methylthio orethanesulfonyl. Substituted phenyl is to be understood as meaningespecially groups such as fluorophenyl, methoxyphenyl, tolyl ortrifluoromethyl, wherein the substituents are preferably in the paraposition.

The halogen compounds (II) used as starting materials are either knowncompounds or can be prepared analogously to known compounds. Numerouscompounds of this type are published, for example, in U.S. Pat. No.4,254,125 and European Published Patent Application No. 0,001,187. Thecompound 2-chloro-6-1-methyl-3-(trifluoromethyl)pyrazol-5-yloxy!pyridine is novel and alsoforms a subject of the present invention.

The process according to the invention is preferentially suitable forthe preparation of amides (I) in which A² is nitrogen and forms apyridine ring with the remaining ring members.

Particularly preferred amides (I) are those in which R¹ is a group ofthe formula --OR, R being as defined above.

Other preferred amides (I) are those in which A¹ is nitrogen and forms apyridine ring with the remaining ring members,

those in which A¹ and A⁵ are nitrogen and form a pyrimidine ring withthe remaining ring members,

those in which A¹ and A⁴ are nitrogen and form a pyrazine ring with theremaining ring members,

and those in which A¹, A³ and A⁵ are nitrogen and form a 1,3,5-triazinering with the remaining ring members.

In the last four classes mentioned, particularly preferred amides arethose in which R² is a group of the formula --OR, R being as definedabove.

Other preferred amides (I) are those in which R is an optionallysubstituted phenyl group. This applies especially to the above mentionedamides with a pyridine, pyrimidine, pyrazine or 1,3,5-triazine ring inwhich R¹ or R² is a group of the formula --OR.

Other preferred amides are those in which R⁶ is hydrogen and R⁷ is anoptionally substituted phenyl group.

Preferred halogen compounds (II) are the chlorine compounds (X is Cl).

Particularly preferred triphenylphosphines (IV) are those in which R⁸ toR¹⁰ are identical and are C₁₋₄ -alkoxy or benzyloxy groups.

The triphenylphosphine in which R⁸ to R¹⁰ are methoxy groups is veryparticularly preferred.

The catalytically active palladium phosphine complex is advantageouslyformed in situ by a process in which palladium in finely dividedelemental form (e.g., palladium on activated charcoal), a Pd(II) salt(e.g., the chloride or the acetate) or a suitable Pd(II) complex e.g.,dichlorobis(triphenylphosphine)palladium(II)! is reacted with thephosphine. The particularly preferred palladium source is palladium(II)acetate. The palladium is preferably used in an amount of 0.02 to 0.2mol percent of Pd(II) or 0.5 to 2 mol percent of Pd(0) (as Pd/C), basedin each case on the halogen compound (II). The phosphine isadvantageously used in excess (based on Pd), preferably in an amount of0.2 to 5 mol percent, again based on the halogen compound (II).

The solvents used can be either relatively non-polar, for example,methylcyclohexane, toluene or xylene, or polar, for example,acetonitrile, tetrahydrofuran, pyridine, butyl acetate,N-methylpyrrolidone, methyl isobutyl ketone or N,N-dimethylacetamide.Particularly good results have been achieved with non-polar solvents,especially with methylcyclohexane or xylene.

The base used is preferably a relatively weak base. This does not needto be soluble in the solvent used. Examples of suitable bases arecarbonates such as sodium or potassium carbonate, (hydrogen-) phosphatessuch as tripotassium phosphate, dipotassium hydrogen phosphate ordisodium hydrogen phosphate, or acetates such as sodium acetate.Particularly good results have been achieved with sodium carbonate ordipotassium hydrogen phosphate.

The reaction temperature is preferably 80° to 250° C.

The carbon monoxide pressure is preferably 1 to 50 bar.

The halogen compounds (II) are advantageously prepared by reacting adihalide of the general formula: ##STR5## in which X is chlorine,bromine or iodine and A¹ to A⁵ are as defined above, with the provisothat one of the radicals R¹ to R⁵ on a carbon atom adjacent to a ringnitrogen atom is Z, Z being chlorine, bromine or iodine, and theremaining radicals R¹ to R⁵, if present, are as defined in claim 1, withan aromatic or heteroaromatic hydroxyl compound of the general formula:

    R--OH                                                      VI,

in which R is an optionally substituted aromatic or heteroaromaticradical.

The following examples illustrate how the process according to theinvention is carried out.

EXAMPLE 1

2-Chloro-6- 3-(trifluoromethyl)phenoxy!pyridine

17.45 g (690 mmol) of sodium hydride (95 percent) was suspended in 420ml of N,N-dimethylacetamide. 106.7 g (658 mmol) of3-(trifluoromethyl)phenol was added dropwise over 2 hours at 15° C. Theresulting phenate solution was added dropwise over 2.5 hours, undernitrogen, to a solution of 162.4 g (1.097 mol) or 2,6-dichloroyridine in330 ml of N,N-dimethylacetamide, heated to 90° C. After a further 3hours of reaction time, the mixture was cooled to room temperature, thesodium chloride which had precipitated out was filtered off and thefiltrate was concentrated. The residue was taken up with toluene and 0.1N hydrochloric acid and the organic phase was washed with saturatedsodium chloride solution and concentrated. The oily residue (ca. 200 g)was distilled under vacuum. The yield was 151.5 g (84 percent) of acolorless oil, content (GC): 99.8 percent. Other data concerning theproduct was:

n_(D) ²⁰ =1.5267

MS; m/z: 273/275; 238; 39

¹ H NMR (CDCl₃): δ=6.84 (d, J=7.8 Hz, 1H); 7.07 (d, J=7.8 Hz, 1H); 7.35(m, 1H); 7.42 (m, 1H); 7.45-7.52 (m, 2H); 7.65 (t, J=7.8 Hz, 1H).

¹³ C NMR (CDCl₃): δ=109.88 (CH); 118.16 (CH); 119.24 (CH); 121.67 (CH);123.74 (CF₃); 124.50 (CH); 130.24 (CH); 132.21 (CCF₃); 141.77 (CH);149.12 (C); 153.89 (C); 162.28 (C).

EXAMPLE 2

3-Chloro-2- 3-(trifluoromethyl)phenoxy!pyridine

7.68 g of sodium hydride dispersion (ca. 50 percent in mineral oil) waswashed with pentane under nitrogen and 100 ml of N,N-dimethylformamidewas then added. 21.92 g (135 mmol) of 3-(trifluoromethyl)phenol wasadded dropwise over 30 minutes at room temperature. The resultingphenate solution was added dropwise over 2 hours, under nitrogen, to asolution of 20.1 g (136 mmol) of 2,3-dichloropyridine in 80 ml ofN,N-dimethylformamide, heated to 120° C. After 3 hours of reaction time,the mixture was cooled to room temperature, the sodium chloride whichhad precipitated out was filtered off and the filtrate was concentrated.The residue was extracted with toluene and 0.1 N hydrochloric acid andthe organic phase was washed with saturated sodium chloride solution andconcentrated. The oily residue was distilled under vacuum. The yield was24.75 g (67 percent) of a colorless oil, content (GC): 99.7 percent.Other data concerning the product was:

B.p._(18mbar) =145°-148° C.

n_(D) ²⁰ =1.5282

MS; m/z: 273/275

¹ H NMR (CDCl₃): δ=6.99 (m,1H); 7.36 (d, 1H); 7.45-7.53 (m, 3H); 7.77(d, 1H); 8.02 (d, 1H).

¹³ C NMR (CDCl₃): δ=118.66 (CH); 119.44 (C); 119.98 (CH); 121.75 (CH);123.78 (CF₃); 124.94 (CH); 130.13 (CH); 132.16 (CCF₃); 139.65 (CH);145.20 (CH); 153.88 (C); 158.51 (C).

EXAMPLE 3

N-(4-Fluorophenyl)-6- 3-(trifluoromethyl)phenoxy!-pyridine-2-carboxamide

10.26 g (37.5 mmol) of 2-chloro-6- 3-(trifluoromethyl)phenoxy!pyridine(content: 99.5 percent, prepared according to Example 1), 6.25 g (56.2mmol) of 4-fluoroaniline, 4.37 g (41.3 mmol) of sodium carbonate, 26.3mg (37.5 μmol) of dichlorobis(triphenylphosphine)palladium(II) and 0.40g (1.125 mmol) of tris(4-methoxyphenyl)phosphine (IV, R⁸ =R⁹ =R¹⁰=methoxy) in 37.5 ml of xylene were placed in an autoclave at roomtemperature. The autoclave was flushed with inert gas, a carbon monoxidepressure of 5 bar was then applied and the mixture was heated to 150° C.The CO pressure was raised to 18 bar and the mixture was stirred for 21hours at 150° C. After cooling to room temperature and depressurization,50 ml of xylene and 50 ml of water were added to the reaction mixture,which was filtered. The aqueous phase was extracted with 25 ml of xyleneand the combined organic phases were washed with 30 ml of water. Neitherunconverted educt nor by-products were detectable by GC in the xylenephase. After distillation of the solvent, the crude product (15.83 g)was obtained in the form of a yellow solid. The crude product waspurified by recrystallization from methylcyclohexane. The yield was12.13 g (86 percent) of a light beige solid. Other data concerning theproduct was:

M.p.: 103°-104.5° C.

MS; m/z: 376 (M⁺), 238

¹ H NMR (CDCl₃): δ=6.99-7.04 (m, 2H); 7.17 (d, J=8.4 Hz, 1H); 7.40 (m,1H); 7.46-7.51 (m, 2H); 7.55-7.63 (m, 3H); 7.93 (t, J=7.8 Hz, 1H); 8.03(d, J=7.8 Hz, 1H); 9.24 (br. m, 1H).

EXAMPLE 4

N-(4-Fluorophenyl)-6- 3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 3 except that thedichlorobis(triphenylphosphine)palladium(II) was replaced with the samemolar amount of palladium(II) acetate. The CO pressure was 19 bar. Thisgave 15.77 g of crude product and, after recrystallization, 11.82 g(83.8 percent) of a colorless solid. The M.p. was 104° to 105° C.

EXAMPLE 5

N-(4-Fluorophenyl)-6- 3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

Analogously to Example 4, 6.84 g (25 mmol) of 2-chloro-6-3-(trifluoromethyl)phenoxy!pyridine, 3.33 g (30 mmol) of4-fluoroaniline, 2.92 g (27.5 mmol) of sodium carbonate, 5.6 mg (25μmol) of palladium(II) acetate and 260 mg (0.75 mmol) oftris(4-methoxyphenyl)phosphine in 25 ml of methylcyclohexane werereacted under a CO pressure of 7.5 bar for 20 hours. After cooling to80° C., the reaction mixture was diluted with 65 ml of warmmethylcyclohexane. The salts were filtered off and washed with 10 ml ofwarm methylcyclohexane. On cooling to 5° C. the product crystallized.The yield was 8.1 g (86 percent) of a light beige solid. The meltingpoint was 104.5° to 105.1° C.

EXAMPLE 6

N-(4-Fluorophenyl)-6- 3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 3 except that thetris(4-methoxyphenyl)phosphine was replaced with the same molar amountof tris(4-methylphenyl)phosphine (IV, R⁸ =R⁹ =R¹⁰ =methyl). The COpressure was 20 bar and the reaction time was 21 hours. The compositionof the dissolved products in the xylene phase was determined by GC. 94.1percent of the title compound and 5.9 percent of educt were found.

EXAMPLE 7

N-(4-Fluorophenyl)-6- 3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 3 except that thetris(4-methoxyphenyl)phosphine was replaced with the same molar amountof tris(4-fluorophenyl)phosphine (IV, R⁸ =R⁹ =R¹⁰ =fluorine). The COpressure was 19 bar and the reaction time was 21 hours. The compositionof the dissolved products in the xylene phase was determined by GC. 90.8percent of the title compound and 9.2 percent of educt were found.

EXAMPLE 8

N-(4-Fluorophenyl)-6- 3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 4 except that thetris(4-methoxyphenyl)phosphine was replaced with the same molar amountof tris(4-benzyloxyphenyl)phosphine (IV, R⁸ =R⁹ =R¹⁰ =benzyloxy). Thecomposition of the dissolved products in the xylene phase was determinedby GC. 99.1 percent of the title compound, 0.5 percent of educt and 0.2percent of N-(4-fluorophenyl)-6-3-(trifluoromethyl)phenoxy!pyridine-2-amine were found.

EXAMPLES 9 TO 12

N-(4-Fluorophenyl)-6- 3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 4 except that the reactiontime was shortened to 6 hours and various solvents were employed. Thecomposition of the dissolved products in the organic phase wasdetermined by GC. The results are compiled in the following Table I.

                  TABLE I    ______________________________________                            4-Fluoroaniline    Solvent      Product  %!                            Educt  %!  %!    ______________________________________    Methylcyclohexane                 87.3        7.2       5.2    Pyridine     79.5        7.7      12.8    N,N-Dimethylacetamide                 74.4       15.0      10.6    Butyl acetate                 72.6       19.8       7.3    ______________________________________

EXAMPLE 13

2-Chloro-6- 1-methyl-3-(trifluoromethyl)pyrazol-5-yloxy!pyridine

1.8 g (71 mmol) of sodium hydride (95 percent) was suspended in 25 ml ofN,N-dimethylacetamide. A solution of 12.46 g (67 mmol) of1-methyl-5-hydroxy-3-(trifluoromethyl)pyrazole (J. Heterocycl. Chem.1990, 27, 243) in 40 ml of N,N-dimethylacetamide was added dropwise over1 hour at 22° C. The resulting solution was added dropwise over 3 hours,under nitrogen, to a solution of 18.5 g (125 mmol) of2,6-dichloropyridine in 37.5 ml of N,N-dimethylacetamide, heated to 135°C. After a further 5 hours of reaction time, the mixture was cooled toroom temperature, the sodium chloride which had precipitated out wasfiltered off and the filtrate was concentrated. The residue was taken upwith toluene and water and the organic phase was washed with saturatedsodium chloride solution and concentrated. The solid residue wasdistilled under vacuum. The title compound distills at 175° C. under 25mbar. This gave 12.5 g of crude product in the form of a yellow solid(96 percent pure, GC). This was purified by recrystallization fromdiisopropyl ether. The yield was 11.55 g (62 percent) of colorlesscrystals, content (GC): 99.9 percent. Other data concerning the productwas:

M.p.: 56°-58° C.

MS; m/z: 277/279

¹ H NMR (CDCl₃): δ=3.80 (s, 3H); 6.40 (s, 1H); 6.96 (d, J=8.2 Hz, 1H);7.18 (d, J=8.2 Hz, 1H); 7.74 (t, J=8.2 Hz, 1H).

EXAMPLE 14

N-(4-Fluorophenyl)-6-1-methyl-3-(trifluoromethyl)pyrazol-5-yloxy!pyridine-2-carboxamide

The procedure was as described in Example 4. 4.92 g of crude product wasobtained in the form of a light yellow solid from 3.47 g (12.5 mmol) of2-chloro-6- 1-methyl-3-(trifluoromethyl)pyrazol-5-yloxy!pyridine, 2.08 g(18.7 mmol) of 4-fluoroaniline, 1.46 g (13.8 mmol) of sodium carbonate,5.6 mg (25 μmol) of palladium(II) acetate and 0.13 g (375 μmol) oftris(4-methoxyphenyl)phosphine in 12.5 ml of xylene after 21 hours at150° C. under a CO pressure of 19 bar (GC: complete conversion). It waspurified by recrystallization from methylcyclohexane. The yield was 3.97g (84.4 percent) of light beige crystals. Other data concerning theproduct was:

M.p.: 138°-139° C.

¹ H NMR (CDCl₃): δ=3.85 (s, 3H); 6.41 (s, 1H); 7.06 (m, 2H); 7.29 (d,J=8.1 Hz, 1H); 7.59 (m, 2H); 8.05 (t, J=8.1 Hz, 1H); 8.14 (d, J=8.1 Hz,1H); 9.28 (bs, 1H).

EXAMPLE 15

N-Phenyl-6- 3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 5 except that the4-fluoroaniline was replaced with 2.79 g (30 mmol) of aniline and theamount of palladium(II) acetate was doubled (50 μmol). The CO pressurewas 19 bar. The yield was 72.8 percent of a beige solid. The meltingpoint was 92° to 93° C. (from methylcyclohexane). Other data concerningthe product was:

MS; m/z: 358 (M⁺), 239; 238; 39 (100 percent)

¹ H NMR (CDCl₃): δ=7.11 (t, J=7.3 Hz, 1H); 7.18 (d, J=8.1 Hz, 1H); 7.33(t, J=7.3 Hz, 2H); 7.41 (m, 1H); 7.52 (m, 2H); 7.55 (m, 1H); 7.59 (m,2H); 7.95 (dd, J=7.3/0.8 Hz, 1H); 8.04 (d, J=7.3 Hz, 1H) 9.27 (br. s,1H).

EXAMPLE 16

N-(3-Fluorophenyl)-6- 3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 15 except that the aniline wasreplaced with 3.33 g (30 mmol) of 3-fluoroaniline. The CO pressure was20 bar. The yield was 73 percent of a beige solid. The melting point was74° to 75° C. (from methylcyclohexane). Other data concerning theproduct was:

MS; m/z: 376 (M⁺); 238; 39 (100 percent)

¹ H NMR (CDCl₃): δ=6.80 (m, 1H); 7.05 (d, J=7 Hz, 1H); 7.19 (d, J=8.1Hz, 1H); 7.25 (m, 1H); 7.41 (m, 1H); 7.54 (m, 2H); 7.60 (m, 2H); 7.96(dd, J=7.3/0.8 Hz, 1H); 8.03 (d, J=7.3 Hz, 1H); 9.31 (br. s, 1H).

EXAMPLE 17

N-(2,4-Difluorophenyl)-6-3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 15 except that the aniline wasreplaced with 3.87 g (30 mmol) of 2,4-difluoroaniline. The CO pressurewas 20 bar. The yield was 80.5 percent of a beige solid. The meltingpoint was 110.5° to 111.5° C. (from methylcyclohexane). Other dataconcerning the product was:

MS; m/z: 394 (M⁺); 238; 39 (100 percent)

¹ H NMR (CDCl₃): δ=6.85 (m, 2H); 7.23 (m, 1H); 7.45 (m, 2H); 7.58 (m,2H); 7.99 (m, 2H); 8.45 (m, 1H); 9.48 (br. s, 1H).

EXAMPLE 18

N- 3-(Trifluoromethyl)phenyl!-6-3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 15 except that the aniline wasreplaced with 5.09 g (30 mmol, 95 percent content) of3-(trifluoromethyl)aniline and 1.2 mmol oftris(4-methoxyphenyl)phosphine was employed. The CO pressure was 20 bar.The yield was 75.4 percent of a beige solid. The melting point was 93.1°to 93.7° C. (from methylcyclohexane). Other data concerning the productwas:

MS; m/z: 426 (M⁺); 238; 39 (100 percent)

¹ H NMR (CDCl₃): δ=7.21 (d, J=8.1 Hz, 1H); 7.37 (m, 1H); 7.43 (m, 2H);7.57 (m, 1H); 7.62 (m, 2H); 7.69 (d, J=8.1 Hz, 1H); 7.82 (s, 1H); 7.96(dd, J=7.3/0.6 Hz, 1H); 8.04 (d, J=7.3 Hz, 1H); 9.39 (br. s, 1H).

EXAMPLE 19

N- 4-(Trifluoromethyl)phenyl!-6-3-(trifluoromethyl)phenoxy!pyridine-2-carboxamide

The procedure was as described in Example 18 except that the3-(trifluoromethyl)aniline was replaced with 4.93 g (30 mmol, 98 percentcontent) of 4-(trifluoromethyl)aniline. The CO pressure was 20 bar. Theyield was 79.6 percent of a beige solid. The melting point was 130.5° to132° C. (from methylcyclohexane). Other data concerning the product was:

MS; m/z: 426 (M⁺); 238; 39 (100 percent)

¹ H NMR (CDCl₃): δ=7.21 (d, J=8.1 Hz, 1H); 7.42 (m, 1H); 7.60 (m, 7H);7.97 (t, J=7.3 Hz, 1H); 8.05 (d, J=7.3 Hz, 1H); 9.41 (br. s, 1H).

EXAMPLE 20

N-(2,2,2-Trifluoroethyl)-6-1-methyl-3-(trifluoromethyl)pyrazol-5-yloxy!pyridine-2-carboxamide

Analogously to Example 14, 1.39 g (5 mmol) of 2-chloro-6-1-methyl-3-(trifluoromethyl)-pyrazol-5-yloxy!pyridine, 0.75 g (7.57mmol, 98 percent content) of 2,2,2-trifluoroethylamine, 0.80 g (7.55mmol) of anhydrous sodium carbonate, 5.6 mg (25 μmol) of palladium(II)acetate and 88 mg (0.25 mmol) of tris(4-methoxyphenyl)phosphine in 20 mlof methylcyclohexane were reacted under a CO pressure of 21 bar. Theyield was 0.96 g (75.4 percent) of a white solid. The melting point was135.8° to 136.3° C. (from methylcyclohexane). Other data concerning theproduct was:

MS; m/z: 368 (M⁺); 242 (100 percent)

¹ H NMR (CDCl₃): δ=3.82 (s, 3H); 4.05 (m, 2H); 6.29 (s, 1H); 7.27 (dt,J=8.1/0.6 Hz, 1H); 7.64 (br. s, 1H); 8.01 (dd, J=7.3/0.5 Hz, 1H); 8.07(d, J=7.3 Hz, 1H).

COMPARATIVE EXAMPLE 1

The procedure was analogous to Example 3 except that thetris(4-methoxyphenyl)phosphine was replaced with the same molar amountof triphenylphosphine. After a reaction time of 15.5 hours at a COpressure of 15 bar, the composition of the dissolved products in thexylene phase was determined by GC. Only 43.2 percent of the desiredproduct and 56.8 percent of unconverted educt were found.

COMPARATIVE EXAMPLE 2

The procedure was as described in Example 3 except that thetris(4-methoxyphenyl)phosphine was replaced with the same molar amountof tri-n-butylphosphine. After a reaction time of 15 hours at a COpressure of 14 bar, the composition of the dissolved products in thexylene phase was determined by GC. Only traces (0.4 percent) of thedesired product and 96.8 percent of unconverted educt were found.

COMPARATIVE EXAMPLE 3

The procedure was as described in Example 3 except that thetris(4-methoxyphenyl)phosphine was replaced with the same molar amountof tris(3-methoxyphenyl)phosphine. After a reaction time of 21 hours ata CO pressure of 19 bar, the composition of the dissolved products inthe xylene phase was determined by GC. Only 53.3 percent of the desiredproduct and 46.7 percent of unconverted educt were found.

COMPARATIVE EXAMPLE 4

The procedure was analogous to Example 3 except that thetris(4-methoxyphenyl)phosphine was replaced with the same molar amountof tris(2-methoxyphenyl)phosphine. After a reaction time of 21 hours ata CO pressure of 19 bar, the composition of the xylene phase wasdetermined by GC. Only unconverted educt was found, with no products atall being found.

COMPARATIVE EXAMPLE 5

The procedure was analogous to Example 3 except that thetris(4-methoxyphenyl)phosphine was replaced with the same molar amountof tris(4-chlorophenyl)phosphine. After a reaction time of 21 hours at aCO pressure of 20 bar, the composition of the dissolved products in thexylene phase was determined by GC. Only 26.3 percent of the desiredproduct and 73.7 percent of unconverted educt were found.

What is claimed is:
 1. A process for the preparation of an amide of theformula: ##STR6## wherein: A¹ is nitrogen or CR¹,A² is nitrogen or CR²,A³ is nitrogen or CR³, A⁴ is nitrogen or CR⁴ and A⁵ is nitrogen or CR⁵,with the proviso that at least one of the ring members A¹ to A⁵ isnitrogen and that two nitrogen atoms are not bonded directly to oneanother; R¹ to R⁵, if present, independently of one another arehydrogen, C₁₋₄ -alkyl or aryl, but one of the substituents R¹ to R⁵ is agroup of the formula --OR, wherein R is an optionally substitutedaromatic or heteroaromatic radical, neither of said substituted radicalsare ones which will undergo alkylation reaction; R⁶ is hydrogen or C₁₋₄-alkyl; and R⁷ is an optionally substituted aromatic or heteroaromaticradical, neither of said substituted radicals are ones which willundergo alkylation reaction, comprising reacting a halogen compound ofthe formula: ##STR7## wherein A¹ to A⁵ are as defined above and X ischlorine, bromine or iodine, directly with carbon monoxide and a primaryor secondary amine of the formula:

    R.sup.6 --NH--R.sup.7                                      III,

wherein R⁶ and R⁷ are as defined above, in the presence of a complex ofpalladium with a triphenylphosphine of the formula: ##STR8## wherein atleast one of R⁸ to R¹⁰ is benzyloxy and the remainder of R⁸ to R¹⁰independently of one another are C₁₋₄ -alkyl, C₁₋₄ -alkoxy or fluorine,and with a base.
 2. The process according to claim 1, wherein A² isnitrogen and part of a pyridine ring.
 3. The process according to claim2, wherein R¹ is a group of the formula --OR, R being an optionallysubstituted aromatic or heteroaromatic radical, neither of said radicalsare ones which will undergo alkylation reaction.
 4. The processaccording to claim 3, wherein R is an optionally substituted phenylgroup, said substituted group is one which will not undergo alkylationreaction.
 5. The process according to claim 1, wherein A¹ is nitrogenand part of a pyridine ring.
 6. The process according to claim 5,wherein R² is a group of the formula --OR, R being an optionallysubstituted aromatic or heteroaromatic radical, neither of saidsubstituted radicals are ones which will undergo alkylation reaction. 7.The process according to claim 1, wherein A¹ and A⁵ are nitrogen andpart of a pyrimidine ring.
 8. The process according to claim 7, whereinR² is a group of the formula --OR, R being an optionally substitutedaromatic or heteroaromatic radical, neither of said substituted radicalsare ones which will undergo alkylation reaction.
 9. The processaccording to claim 1, wherein A¹ and A⁴ are nitrogen and part of apyrazine ring.
 10. The process according to claim 9, wherein R² is agroup of the formula --OR, R being an optionally substituted aromatic orheteroaromatic radical, neither of said substituted radicals are oneswhich will undergo alkylation reaction.
 11. The process according toclaim 1, wherein A¹, A³ and A⁵ are nitrogen.
 12. The process accordingto claim 11, wherein R² is a group of the formula --OR, R being anoptionally substituted aromatic or heteroaromatic radical, neither ofsaid substituted radicals are ones which will undergo alkylationreaction.
 13. The process according to claim 12, wherein R is anoptionally substituted phenyl group, said substituted group is one whichwill not undergo alkylation reaction.
 14. The process according to claim12, wherein R⁶ is hydrogen and R⁷ is an optionally substituted phenylgroup, said substituted group is one which will not undergo alkylationreaction.
 15. The process according to claim 14, wherein X is chlorine.16. The process according to claim 15, wherein R⁸ to R¹⁰ are identicaland are benzyloxy groups.
 17. The process according to claim 1, whereinR⁶ is hydrogen and R⁷ is an optionally substituted phenyl group, saidsubstituted group is one which will not undergo alkylation reaction. 18.The process according to claim 1, wherein X is chlorine.
 19. The processaccording to claim 1, wherein R⁸ to R¹⁰ are identical and are C₁₋₄-alkoxy or benzyloxy groups.
 20. A process for the preparation of anamide of the formula: ##STR9## wherein: A¹ is nitrogen or CR¹,A² isnitrogen or CR², A³ is nitrogen or CR³, A⁴ is nitrogen or CR⁴ and A⁵ isnitrogen or CR⁵, with the proviso that at least one of the ring membersA¹ to A⁵ is nitrogen and that two nitrogen atoms are not bonded directlyto one another; R¹ to R⁵, if present, independently of one another arehydrogen, C₁₋₄ -alkyl or aryl, but one of the substituents R¹ to R⁵ is agroup of the formula --OR, wherein R is an optionally substitutedaromatic or heteroaromatic radical, neither of said substituted radicalsare ones which will undergo alkylation reaction; R⁶ is hydrogen or C₁₋₄-alkyl; and R⁷ is an optionally substituted aromatic or heteroaromaticradical, neither of said substituted radicals are ones which willundergo alkylation reaction, comprising, in a first step, reacting adihalide of the general formula: ##STR10## wherein A¹ to A⁵ are asdefined above, X is chlorine, bromine or iodine, one of the radicals R¹to R⁵ on a carbon atoms adjacent to a ring nitrogen atom is Z, Z beingchlorine, bromine or iodine, and the remaining radicals R¹ to R⁵, ifpresent, are as defined above, with an aromatic or heteroaromatichydroxyl compound of the formula:

    R--OH                                                      VI,

wherein R is as defined above, to give a (hetero)aryloxy halogencompound of the formula: ##STR11## wherein A¹ to A⁵, R and X are asdefined above, and, in a second step, reacting said product of formulaII with carbon monoxide and an amine of the formula:

    R.sup.6 --NH--R.sup.7                                      III,

wherein R⁶ and R⁷ are as defined above, in the presence of a complex ofpalladium with a triphenylphosphine of the formula: ##STR12## wherein atleast one of R⁸ to R¹⁰ is benzyloxy and the remainder of R⁸ to R¹⁰independently of one another are C₁₋₄ -alkyl, C₁₋₄ -alkoxy or fluorine,and with a base.
 21. The process according to claim 20, wherein A² isnitrogen and part of a pyridine ring.
 22. The process according to claim21, wherein R¹ is a group of the formula --OR, R being an optionallysubstituted aromatic or heteroaromatic radical, neither of saidsubstituted radicals are ones which will undergo alkylation reaction.23. The process according to claim 22, wherein R is an optionallysubstituted phenyl group, said substituted group is one which will notundergo alkylation reaction.
 24. The process according to claim 20,wherein A¹ is nitrogen and part of a pyridine ring.
 25. The processaccording to claim 24, wherein R² is a group of the formula --OR, Rbeing an optionally substituted aromatic or heteroaromatic radical,neither of said substituted radicals are ones which will undergoalkylation reaction.
 26. The process according to claim 20, wherein A¹and A⁵ are nitrogen and part of a pyrimidine ring.
 27. The processaccording to claim 26, wherein R² is a group of the formula --OR, Rbeing an optionally substituted aromatic or heteroaromatic radical,neither of said substituted radicals are ones which will undergoalkylation reaction.
 28. The process according to claim 20, wherein A¹and A⁵ are nitrogen and part of a pyrazine ring.
 29. The processaccording to claim 28, wherein R² is a group of the formula --OR, Rbeing an optionally substituted aromatic or heteroaromatic radical,neither of said substituted radicals are ones which will undergoalkylation reaction.
 30. The process according to claim 20, wherein A¹,A³ and A⁵ are nitrogen.
 31. The process according to claim 30, whereinR² is a group of the formula --OR, R being an optionally substitutedaromatic or heteroaromatic radical, neither of said substituted radicalsare ones which will undergo alkylation reaction.
 32. The processaccording to claim 31, wherein R is an optionally substituted phenylgroup, said substituted group is one which will not undergo alkylationreaction.
 33. The process according to claim 31, wherein R⁶ is hydrogenand R⁷ is an optionally substituted phenyl group, said substituted groupis one which will not undergo alkylation reaction.
 34. The processaccording to claim 33, wherein X is chlorine.
 35. The process accordingto claim 34, wherein R⁸ to R¹⁰ are identical and are benzyloxy groups.36. The process according to claim 20, wherein R⁶ is hydrogen and R⁷ isan optionally substituted phenyl group, said substituted group is onewhich will not undergo alkylation reaction.
 37. The process according toclaim 20, wherein X is chlorine.
 38. The process according to claim 20,wherein R⁸ to R¹⁰ are identical and are C₁₋₄ -alkoxy or benzyloxygroups.